G-protein Coupled Receptors and 7-TM Receptors

<p>Gemilukast (ONO-6950) is a cysteinyl leukotriene 1 and 2 receptor inhibitor that inhibits bronchoconstriction and is used in the treatment of asthma.</p>

Nifeviroc (TD-0232) is an orally active CCR5 antagonist, useful in HIV-1 infection research.

CGRP antagonist 7 is a potent calcitonin gene-related peptide receptor (CGRP) antagonist with a Ki value of 0.029 nM. It effectively inhibits CGRP receptor-mediated cyclic adenosine monophosphate (cAMP) production, with an IC50 value of 1.5 nM. This compound is useful in migraine research.

Selective, high affinity competitive antagonist of the P2Y1 receptor

Kendomycin is a proteasome inhibitor and endothelin receptor antagonist. It induces apoptosis in lymphoma.

NK-1 Antagonist 1 is a NK-1 receptor antagonist.

<p>SGLT1/2-IN-8 (compound 8) is a potent and orally active dual inhibitor of SGLT1/2, exhibiting IC50 values of 4 nM and 1 nM, respectively. It shows antihyperglycemic properties, making it suitable for related research.</p>

CVT-5440 is a selective, high-affinity (2B) adenosine receptor antagonist with good selectivity.

(Rac)-BI 703704 is a potent activator of soluble guanylyl cyclase (sGC).

8 Hydroxy PIPAT oxalate is a selective 5-HT1A receptor agonist that enhances the spontaneous release of histamine by promoting the degranulation of mast cells in guinea pig and human intestinal preparations. By activating the serotonin signaling pathway, this compound demonstrates potential in regulating gastrointestinal functions and offers insight into the management and suppression of functional gastrointestinal disorders such as irritable bowel syndrome. Its effects in increasing histamine release could play a crucial role in gastrointestinal regulation.

<p>SphK2-IN-1 is an SphK2 inhibitor with an IC50 value of 0.359 μM. SphK2-IN-1 can be used to study cancer, inflammation, neurological and cardiovascular diseases.</p>

RS 12254 is a dopamine agonist and antihypertensive agent.

<p>Metrazoline (o-Methyl-tracizoline) acts as a ligand for adrenergic receptors (low affinity) and imidazoline I2 receptors.</p>

CCR7-Cmp2105 is a thiadiazole-dioxide allosteric antagonist for CCR7 with a Kd of 3 nM and IC50 of 7.3 μM against arrestin binding.

MRS2279 diammonium, a P2Y1 antagonist with K i 2.5 nM, IC 50 51.6 nM, blocks ADP-induced platelet aggregation, pK b 8.05.

Iloprost, a potent prostacyclin analog, binds to human IP & EP1 receptors with high affinity; inhibits platelet aggregation effectively.

BMS-986120: Oral, reversible PAR4 antagonist. IC50: 9.5 nM (human), 2.1 nM (monkey). Potent, selective antiplatelet.

Lisuride: an oral D2 dopamine agonist, ergot derivative, used in Parkinson's, migraine, and high prolactin research.

Nedocromil sodium is a pharmacologic stabilizer of mast cells, has been shown to normalize cytokine levels and attenuate cardiac remodeling.

S1P1 agonist 4 exhibits enhanced potency with an EC 50 value of less than 0.05 mg/kg and a predicted human half-life (t1/2) of approximately 5 days, indicating

AM11638 is an endogenous cannabinoid analogue that targets cannabinoid receptors (CB1 and CB2 receptors), exhibiting analgesic properties. It shows potential for research in neurological disorders and inflammation-related diseases.

OP-2507, a prostacyclin agonist, is used potentially for the treatment of hepatic insufficiency and hypertension.

<p>SEP-363856 (SEP-856) mesylate is an orally active compound that acts as an agonist for both TAAR1 and 5-HT1A receptors. This compound exhibits antipsychotic activity in the central nervous system and has potential for the study of schizophrenia.</p>

<p>Sulamserod hydrochloride is a 5-HT4 receptor antagonist. It is utilized in research related to gastrointestinal disorders.</p>

GLP-1R modulator-1 (Compound 384) is a potent and orally active selective agonist of the glucagon-like peptide-1 receptor (GLP-1R). It activates G protein-coupled signaling, leading to increased intracellular cAMP levels, enhanced insulin secretion, delayed gastric emptying, and reduced appetite. GLP-1R modulator-1 holds potential for research in type 2 diabetes, obesity, and non-alcoholic steatohepatitis (NASH).

(S)-Bucindolol is an enantiomer of bucindolol, specifically a β1-adrenergic receptor antagonist. It is primarily utilized in research related to heart failure.

<p>Rodatristat ethyl is an oral TPH1 inhibitor reducing 5-HT levels &amp; lowering PAH at low doses.</p>

N-methyl LTC4 is a stable synthetic analog of LTC4 and a selective CysLT2 agonist, useful in studying leukotriene pharmacology.

Disulergine is a dopamine receptor agonist. It also prolactin release-inhibiting 8 alpha-amino-ergoline.

MK-8825 is a CGRP receptor antagonist.

<p>Serotonin hydrogen maleate serves as a monoaminergic neurotransmitter and an endogenous 5-HT receptor agonist within the central nervous system (CNS). It also functions as an inhibitor of catechol O-methyltransferase (COMT), exhibiting a Ki value of 44 μM.</p>

Flucopride (Compound 4a) acts as an acetylcholinesterase inhibitor (AChE) with an IC50 value of 24 nM and serves as a partial agonist for the human 5-HT4 receptor (5-HT4R) with a Ki of 9.6 nM for (h)5-HT4R. It promotes non-amyloidogenic processing of APP in COS-7 cells transiently expressing (h)5-HT4R with an EC50 of 23.0 nM. Flucopride is also likely to exhibit significant gastrointestinal tract (GIT) penetration and blood-brain barrier (BBB) permeability, as determined in PAMPA experiments.

Butopamine hydrochloride is an orally active inotropic compound that is more effective at increasing heart rate compared to Dobutamine.

<p>RTIOXA-43 is an OX2R/OX1R (orexin receptor) dual agonist that increases wakefulnesand is commonly used in studies related to narcolepsy and neural signaling.</p>

LX2761 is a stable inhibitor for SGLT1/2 with IC50s of 2.2/2.7 nM; it targets SGLT1 in the GI tract.

DNA crosslinker 6 (compound 1) is an anti-mitotic agent known for its strong binding affinity to AT-DNA and inhibition of AT-hook 1 binding to DNA (IC50=0.03 µM). Additionally, it exhibits anti-protozoal activity, effectively inhibiting T. brucei with an EC50 of 0.83 µM.

Meluadrine, a potent agonist of the β2 adrenergic receptor, is one of the metabolites of Tulobuterol [1].

BMS-986104 is a potent and selective S1P1 receptor modulator.

Macitentan n-butyl analogue, an oral ETA/ETB receptor blocker, may treat IPF and PAH.

5-HT7R antagonist 1 is a G protein-biased antagonist with Ki of 6.5 nM for 5-HT 7R.

5-HT6R/MAO-B modulator 1 blocks 5-HT6R and permanently inhibits MAO-B, protects glial cells, and reverses memory loss.

<p>CHF-6366: M3 antagonist &amp; β2 agonist (pKi 10.4/11.4), mild Ca channel blocker, used in COPD study.</p>

5-HT2A receptor agonist-8 (compound 8) is a potent 5-HT2A receptor agonist with an EC50 of 0.6784 nM. It is suitable for research related to depression and bipolar disorder.

RF9 hydrochloride is a potent and selective Neuropeptide FF receptor antagonist that acts on hNPFF1R (Ki: 58 nM) and hNPFF2R (Ki: 7 nM).

<p>VA012 (compound 11) acts as a positive allosteric modulator (PAM) of the serotonin 5-HT2C receptor. It has been shown to reduce food intake and prevent weight gain during subchronic administration without causing central nervous system-related discomfort. VA012 is applicable in obesity research.</p>

OX2R agonist 1 is an OX2R activator with an EC50 of less than 100 nM. It is utilized in research related to narcolepsy and cataplexy.

GPR27 agonist-1 (compound I) is a selective agonist for GPR27 with a pEC50 value of 6.34.

<p>Methacycline, a tetracycline antibiotic, inhibits bacterial protein synthesis and effectively suppresses epithelial-mesenchymal transition (EMT). It blocks EMT in vitro and inhibits fibrogenesis in vivo without directly affecting the TGF-β1Smad signaling pathway. As an antimicrobial agent, Methacycline holds potential for research in pulmonary fibrosis.</p>

PD 140376: Selective CCK-B/gastrin receptor antagonist radioligand for guinea pig stomach & brain.

LTB4 is a leukocyte-activating fatty acid via 5-lipoxygenase. Two receptors, BLT1 and BLT2, bind it. 14,15-dehydro LTB4 is a stronger BLT1 antagonist.

TAK-661 is an inhibitor of eosinophil chemotaxis (eosinophil chemotaxis) that significantly alleviates late-phase bronchoconstriction while inhibiting the proliferation of eosinophils in bronchoalveolar lavage (BAL) and their infiltration into the airway walls.

<p>AFP-07 is a highly selective and potent agonist. It was used for the prostacyclin receptor.</p>

<p>S1PR1 agonist 1 is a potent agonist of S1PR1. S1PR1 agonist 1 has potential in autoimmune diseases.</p>

Oral CCR1 antagonist A1B1 targets h/m/rCCR1 (IC50: 0.03/0.58/0.32 μM), potential for treating inflammatory diseases.

Substituted piperidines-1 can promote the release of growth hormone in humans and animals.

Taprostene (CG-4203), a stable Prostacyclin analogue, protects endothelium and myocardium post-ischemia in cats, with minimal hemodynamic impact.

<p>BI-113823 is an orally active and selective bradykinin B1 receptor antagonist. It alleviates mechanical hyperalgesia induced by complete Freund's adjuvant in rats. BI-113823 is applicable for research on chronic inflammatory pain.</p>

<p>Zaladenant is an adenosine receptor antagonist with antitumor properties.</p>

<p>25B-NBOH hydrochloride is a phenethylamine that exhibits high affinity for serotonin (5-HT) receptors 5-HT2A and 5-HT2C, with pKi values of 8.3 and 9.4, respectively.</p>

D3/5-HT receptor modulator-1 (compound 5i) is a selective antagonist of the dopamine D3 and 5-HT2A receptors, and a partial agonist at the 5-HT1A receptor. It exhibits Ki values of 4.5 nM, 11.9 nM, and 15.3 nM for the dopamine D3, 5-HT2A, and 5-HT1A receptors respectively. The compound shows lower affinity for the dopamine D2 receptor, 5-HT2C receptor, and hERG channel. D3/5-HT receptor modulator-1 possesses atypical antipsychotic properties.

H3R-IN-1 is an effective inverse agonist of the histamine receptor 3 (H3R).

MRS4865 (compound 7a) serves as a chimeric antagonist for the P2Y14 receptor and an agonist for UDP-glucose, offering protection against neuropathic pain.

Monohydroxy Netupitant is a highly selective antagonist of NK1 receptor, and is Netupitant metabolite.

INCB-9471 HCl: a potent CCR5 antagonist, blocks monocyte migration & HIV-1.

Tonapofylline, orally active, selectively blocks A1 adenosine receptor (Ki: 7.4 nM), used in heart failure research.

<p>TAAR1 agonist 2 (compound 30), a full agonist at trace amine-associated receptor 1 (TAAR1) (pEC50=7.5), also displays agonistic properties at H1 receptors and activates various muscarinic acetylcholine receptors, including the M2 receptor (pEC50=5). This compound is utilized in researching neuropsychiatric diseases.</p>

GRPR antagonist-1 targets GRPR, kills specific cancer cells (e.g., PC3, Pan02, HGC-27), and promotes apoptosis by modulating Bcl-2 and Bax.

Nocloprost (SH 475) is a prostaglandin E2 (PGE2) analog, an EP1 and EP3 receptor agonist with local gastric protection and ulcer healing effects.

MRS7799 is a selective A3 Adenosine Receptor antagonist with Kd values of 0.55 nM for humans, 3.74 nM for mice, and 2.80 nM for rats. MRS7799 can be utilized in research related to neurodegenerative diseases, cancer, cardiac and cerebral ischemia, and autoimmune inflammatory diseases.

CTW0404 is an effective positive allosteric modulator (PAM) of the 5-HT receptor, with promising implications for research into neuropsychiatric disorders.

<p>Compound 10 is a potent dual A1/A3 AR antagonist, with Ki values of 37.6 nM (hA1), 25.4 nM (hA3), and 1.47 nM (rA1), studied in renal, lung, and Alzheimer's.</p>

Compound 18g, a potent A1AR blocker with Ki: 2.08 nM (hA1), 6.91 nM (hA2A), 31.2 nM (hA2B).

GAT564, an allosteric CB1R modulator, shows EC50s of 87 nM (cAMP) & 320 nM (β-arrestin2) and lowers IOP effectively in glaucoma mice.

Rocavorexant is an antagonist of the orexin-1 receptor (orexin-1 receptor), exhibiting a pIC50 value of 9.1 for human OX1 and a pIC50 of 6.0 for human OX2.

(S)-Praziquantel is the inactive isomer of R-praziquantel.

PSB-KK1415 is a selective agonist for the human orphan G protein-coupled receptor GPR18, with an EC50 of 19.1 nM.

<p>MRT-92 is an antagonist of Smoothened (Smo) with anti-cancer activity, featuring a binding affinity (Ki) of 0.7 nM. It inhibits the Hedgehog signaling pathway by obstructing the overlapping binding sites within the transmembrane domain of the Smoothened receptor and suppresses the proliferation of cerebellar granule cells in rodents (IC50=0.4 nM). MRT-92 is utilized for research into cerebellar gliomas.</p>

<p>CM699 is an effective dual inhibitor of the dopamine transporter (DAT) and Sigma receptor (σR), with IC50 values of 311 nM and 14.1 nM, respectively.</p>

SB 243213 dihydrochloride is an orally active, selective and high-affinity antagonist of 5-hydroxytryptamine (5-HT)2C receptor(pKi of 9.37 and a pKb of 9.8 for

<p>Fasitibant is a potent and selective nonpeptide kinin B2 receptor antagonist.</p>

IRL 2500 is an antagonist of Endothelin receptor with IC50s of 1.3 and 94 nM for Endothelin A receptor and Endothelin B receptor.

AFP 07 free acid is a 7,7-difluoroprostacyclin derivative. It also acts as a selective and highly potent agonist for the IP receptor.

<p>K-14585 blocks PAR(2), reduces NFkappaB activity, and IL-8 response, but alone can boost IL-8.</p>

CCR5 antagonist 1 is a CCR5 antagonist extracted from WO 2004054974 A2. It can inhibit HIV replication.

BI 639667, an azaindazole-class compound, potently inhibits CCR1 (IC50=1.8 nM in calcium flux assays).

M1069 is an oral A2A/A2B receptor antagonist, 100x more selective over A1/A3, with antitumor properties by blocking adenosine's immunosuppressive effects.

LPA2 antagonist 6 (example 2) acts as an antagonist of Lp(a). It inhibits the formation of Lp(a) with an IC50 value of 2.33 nM, making it useful for cardiovascular disease research.

MrgprX2 antagonist-7 is an anti-allergic agent with significant anti-allergic effects and inhibits mast cell degranulation.

LTF4, made in vitro from LTE4 with enzymes, contracts vascular muscle weakly; potency is LTD4 > LTC4 > LTE4 >> LTF4.

Sitamaquine hydrochloride (WR 6026) is an orally active 8-aminoquinoline analog with antileishmanial activity. This compound inhibits mitochondrial complex II (succinate dehydrogenase) and is characterized by its lipophilic weak base properties. It rapidly accumulates in the acidic compartments of Leishmania parasites, predominantly localizing within the acidocalcisomes.

LY 245769 is an inhibitor of leukotriene E4 (LTE4).

RXFP1 receptor agonist-10 (Compound 188) is an RXFP1 receptor agonist with an EC50 of 0.5 nM. It is useful for research into heart failure.

Bzo-poxizid is a synthetic cannabinoid and a psychoactive substance.

L-365260 hemihydrate: selective oral CCK-B/gastrin blocker, Ki=1.9/2.0 nM, competes with guinea pig receptors.

Butaprost: EP2 receptor agonist, EC50=33 nM, Ki=2.4 μM (murine), reduces fibrosis via TGF-β/Smad2.

CB1/2 receptor-1 (compound 5.3) serves as an agonist for CB1/2 receptors and is utilized in angiogenesis research.

LY3154207: selective, potent oral human dopamine D1 receptor PAM, low agonist activity, EC50=3 nM.

<p>Toladryl is a derivative of Diphenhydramine that can cross the blood-brain barrier and exhibits oral activity, with antihistamine and anticholinergic properties. Its anticholinergic effects are approximately a tenth of those seen with Diphenhydramine, yet it offers 2-4 times the protection against lethal doses of histamine in guinea pigs. The side effects of Toladryl are fewer and milder compared to Diphenhydramine; however, at higher doses, it may cause symptoms such as insomnia, agitation, and disorientation related to the central nervous system. Toladryl is utilized in the research of allergic diseases.</p>

Fosrolapitant is an antagonist of the neurokinin 1 (NK1) receptor.

<p>Compound (−)-19, also known as (-)-5-HT2C agonist-3, is a selective 5-HT2C agonist exhibiting a preference for Gq signaling. It demonstrates efficiency with EC50 values for 5-HT2 receptor subtypes as follows: 5-HT2C at 103 nM, 5-HT2B at 570 nM, and 5-HT2A at 72 nM. This compound is utilized in research on antipsychotics.</p>